A group of neurological diseases in which degeneration of neural cells is involved, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), Huntington's disease, Parkinson's disease, Alzheimer's disease, dementia after a cerebrovascular disorder, and dementia accompanying other neurological deficits, is generally called neurodegenerative diseases. Almost all the neurodegenerative diseases have no established fundamental therapeutic method and thus research for therapeutic method has been desired.
For example, as a therapeutic approach for neurodegenerative disease, administration of a factor suppressing degeneration of nerve cells is conceivable. Administration of a factor suppressing neurodegeneration is expected to bring an advantageous effect on therapy and prevention of such disease. However, such a factor, which can be actually and effectively used as a therapeutic agent, has virtually not been found.
As the factor suppressing degeneration of nerve cells, for example, it is known that a certain type of dopamine receptor agonist possibly has such a function. However, whether there is a causal relation between dopamine antagonism and suppression of nerve-cell degeneration is not known. In addition, it has not always been true that all dopamine receptor agonists have such a function.
In contrast, as a modifying factor for the severity of spinal muscular atrophy (SMA), one of intractable neurodegenerative diseases of the lower motor neuron, a neuronal apoptosis inhibitory protein (NAIP) gene was isolated from human chromosomal 5q13.1 region (see Non Patent Literature 1) and the entire amino acid sequence of NAIP and cDNA encoding NAIP were isolated (see Patent Literature 1). In addition, it was found that, in the process for searching a substance increasing NAIP production, some dopamine receptor antagonists increase the NAIP production, and that these can actually suppress neural degeneration (see Patent Literature 2). Furthermore, it is known that similar dopamine receptor antagonists can protect nerve cells and non-nerve cells from apoptosis caused by oxidative stress and suppress nerve cell death caused by ischemia (see Non Patent Literature 2).
Based on the oxidative stress hypothesis, clinical studies using vitamin E, creatine and others were carried out, however, all attempts failed. In the circumstance, various types of active compounds which increase endogenous NAIP production and suppress oxidative stress-mediated cell death were found (see Patent Literature 3, for example, a compound represented by the following formula (X)).

In the meantime, to sufficiently show the efficacy of a medicinal substance in treating neurological disease, particularly brain neurodegenerative disease, bioavailability thereof must be high. As a more preferred property, blood-brain barrier permeability is desirably high. However, even the aforementioned various types of active compounds capable of suppressing oxidative stress-mediated cell death still have much to be improved, in view of improvement of the solubility and further improvement of the blood-brain barrier permeability.